1979, British Journal of Radiology, 52, 1005
Correspondence (The Editors do not hold themselves responsible for opinions expressed by correspondents)
SI units and dimensions of NSD THE EDITOR—SIR,
I think first it is questionable whether the "unit" of NSD—ret—should be so dignified. It is not a physical quantity but a biological effect and, as such, depends on factors the effect of which cannot at present be measured. The dimensions of rad are ML2T~2 M i.e. squared velocity or length times acceleration. The dimensions of ret are (rad/T 011 ), L2T~189. This is for a definite tolerance level which may vary from centre to centre and from one tissue to another. The biological effect of radiation is of two types: 1, that on the normal tissues to which the NSD concept was meant to apply, and 2, that on tumour cells (TSD in ren). The difference between these effects is in the effect of homeostatic control to which the factor T 0 1 1 applies. Besides this, time-lapse allows of recovery by division of cells in both normal tissues and malignant tumours and, as said in the first publication about the NSD concept (Ellis, 1967), this type of recovery does not depend on the essential difference between normal and malignant cells and therefore does not enter into the NSD formula which was derived utilizing that difference. Instead, this type of recovery by cell-division, common to both types of cell, which is uncertain as to the time of its commencement and the rate at which it proceeds, is probably dependent on nutrition, cell-cycle time, oxygenation, temperature and other things so that a full equation should probably be Biological Effect = Dose (rad) Time x F? where F is an unknown and complex factor. The NSD concept being an attempt to separate fractionation from the effect of time in delivering the radiation was clearly a simplified and incomplete theory but its units are nevertheless more complex than those of the rad. On the other hand, the ren has the same dimensions as the rad. The T D F simplification of the NSD concept depends on the NSD formula and on the principle of proportional tolerance embodied in the NSD concept. For example, using the formula, 15 X 200 rad five times a week gives 1127 ret. Twice this is 2254 ret. On the other hand, 30 X 200 five times a week gives 1768 ret. Since the NSD represents a tolerance level, then in comparison wTith 30 fractions at the same rate 1 5 fractions is half the course and £ + £•= 1. To avoid confusion due to imperfect understanding of this proportional (or partial) tolerance principle, the Time Dose Fractionation modification was developed (Orton and Ellis, 1973). TDF = 10- 3 «J l - 538 x- 0169 where x=T/N. The T D F values for various schedules and parts of courses can be added in such a way as to represent similar effects even when adding the effects of fractionated and continuous radiation. The "dimensions" of TDF are: (L2T'~2)1-538(T~0-169) i.e. L 3076 T~ 3 - 245 - -a difficult medical pill for the physicist to swallow. Yours, etc., The Old Bakery, Thames Street, Charlbury, Oxford OX7 3QQ. (Received May 1979)
F. ELLIS.
REFERENCES ELLIS, F., 1967. Fractionation in Radiotherapy. In Modern Trends in Radiotherapy. Ed. Deeley and Wood. Vol. 1 (Butterworth, London). ORTON, C. G. and ELLIS, F., 1973. A simplification in the
use of the NSD in practical radiotherapy. British Journal of Radiology, 46, 529-537.
SI units and dimensions of NSD THE EDITOR—SIR,
My recent letter on the above subject (Greening, 1978) has brought me correspondence from Dr. D. Bewley, Dr. M. Day and Dr. F. Ellis as a result of which I wish to make a small correction to my letter. I wrote: "£> = NSD where t is time and te is a standard value of time. When te is equal to one day y takes the value 0.11." It is this last sentence that is incorrect, as y = 0.11 whatever the standard value of time chosen. I must hasten to add that this does not affect my argument about the dimensions of NSD or the SI units in which it should be expressed. Yours, etc., J. R. GREENING.
The Department of Medical Physics and Medical Engineering, Royal Infirmary, Edinburgh, EH3 9YW. (Received September 1979) REFERENCE GREENING, J. R., 1978. SI units and dimensions of NSD, CRE and TDF. British Journal of Radiology, 5/, 1026.
Biliary rhabdomyosarcoma of childhood THE EDITOR—SIR,
I read with interest the report by Cannon et al., (1979) emphasizing the role of percutaneous transhepatic cholangiography (PTC) in the management of biliary rhabdomyosarcoma of childhood. While agreeing about the importance of early diagnosis of biliary obstruction and particularly of childhood rhabdomyosarcoma, I should like to emphasize the role of less invasive radiological procedures in the management of this rare tumour of childhood. Recently I have seen two young children with rhabdomyosarcoma of the bile ducts. The first had hepatomegaly and had been jaundiced for six weeks when an ultrasound scan showed dilatation of the bile ducts and gall-bladder. Barium studies and PTC were then undertaken to help define the nature and the extent of the obstructing lesion prior to surgery. The appearances on PTC were similar to those described in the case reported by Cannon et al. (1979). The second child had marked hepatic enlargement and had been jaundiced for ten weeks prior to ultrasound scan. This scan showed that the right lobe of the liver had been completely replaced by an enormous mass containing complex echoes resembling "swiss cheese", (Fig. 1). A technetium sulphur colloid scan showed that the mass was intrahepatic, a point not clearly shown on the ultrasound scan. This patient proceeded to subtotal hepatectomy
1005
1979, British Journal of Radiology, 52, 1006
DECEMBER 1979
Correspondence
FIG. 1. Transverse ultrasound scan of the abdomen 7.0 cm above the iliac crest. The mass containing complex echoes and replacing the right lobe of the liver is shown (white arrow), and normal parenchyma in the left lobe of the liver is also shown (black arrow).
without resort to PTC. Indeed had such a procedure been carried out prior to the ultrasound scan the cholangiography needle inevitably would have entered the tumour rather than the bile ducts. Yours, etc., J. B. WITCOMBE.
The Department of Diagnostic Radiology, The Medical School, Oxford Road, Manchester M13 9PT. {Received February 1979)
R. P. HILL, R. S. BUSH.
REFERENCE CANNON, P. M., LEGGE, D. A. and O'DONNELL, B.,
animals anaesthesia with nembutal and, to a smaller extent, urethane can reduce the radiation response of the KHT sarcoma probably as a result of changes in tumour oxygenation. Sheldon et al. (1977) have also shown that nembutal anaesthesia protects the "MT" mouse tumour against radiation damage although in their case protection was greater than could be explained by changes in tumour oxygenation alone. Conversely Suit et al. (1972) found no effect of nembutal anaesthesia when studying a mammary tumour irradiated in air-breathing mice although this may have been because they used a ten-fraction regime. We proposed (Milne et al., 1973) that one explanation for the anomalous effect of anaesthesia during HPO breathing could be that the anaesthesia prevented, wholly or partially, the vasoconstriction which can result from HPO breathing. The difference between the two anaesthetics observed in our experiments could then be explained by the other physiological parameters discussed above which change to a much greater extent following anaesthesia with nembutal than urethane. Suit et al. (1979) suggest in their letter that the vasoconstriction hypothesis is unlikely to explain their results because they found an enhancement factor (TCD50 air/TCDso HPO) of only 1.1 for single dose irradiation under nembutal anaesthesia. We think that this small effect is probably due to the other confounding factors mentioned above and that vasoconstriction and its inhibition by anaesthesia is the major reason for the difference between the results for animals breathing air or HPO. We would agree with Suit et al. (1979) that the clinical experience with HPO may well have been adversely affected by the change from anaesthetized to non-anaesthetized patients, but our results indicate that, because of the interacting physiological factors discussed above, barbiturates are unlikely to be the most appropriate choice for any new study of the role of anaesthesia in the clinical combination of HPO and radiation therapy. Yours, etc.,
1979.
The use of percutaneous transhepatic cholangiography in a case of embryonal rhabdomyosarcoma. British Journal of Radiology, 52, 326-327.
Ontario Cancer Institute, incorporating the Princess Margaret Hospital, 500 Sherbourne Street, Toronto, Ontario, Canada M4X 1K9. {Received May 1979) REFERENCES JOHNSON, R., FOWLER, J. F. and ZANELLI, G. D.,
1976.
Changes in mouse blood pressure, tumor blood flow and core and tumor temperatures following nembutal and urethane anaesthesia. Radiology, 118, 697—703. KRUUV, J. A., INCH, W. R. and MCCREDIE, J. A.,
1967.
Blood flow and oxygenation of tumours in mice. I. Effects of breathing gases containing carbon dioxide at atmospheric pressure. Cancer, 20, 51-70.
Anaesthesia and efficacy of hyperbaric oxygen in radiation therapy THE EDITOR—SIR,
The data presented by Suit et al. in their recent letter (1979) demonstrate one effect that nembutal anaesthesia can have on the radiation response of tumours. Their results are in agreement with our findings from a number of years ago (Milne et al., 1973) that in comparison to no anaesthesia both nembutal and urethane improved oxygenation in the KHT sarcoma when the host animal breathed oxygen at 200 kPa (HPO), with urethane giving a greater improvement than nembutal. This result may be considered somewhat surprising since barbiturates affect the heart and respiration rates of mice and reduce peripheral blood flow and body temperature (Kruuv et al., 1967; Johnson et al., 1976), factors which could lead to a reduction in tumour oxygenation. Indeed we have results (unpublished) indicating that in air-breathing
MILNE, N., HILL, R. P. and BUSH, R. S., 1973.
Factors
affecting hypoxic KHT tumour cells in mice breathing O2, O2 + CO2, or hyperbaric oxygen with or without anaesthesia. Radiology, 106, 663-671. SHELDON, P. W., HILL, S. A. and MOULDER, J. E.,
1977.
Radioprotection by pentobarbitone sodium of a murine tumour in vivo. International Journal Radiation Biology, 32, 571-575. SUIT, H.
D.,
MARSHALL, N.
and
WOERNER, D.,
1972.
Oxygen, oxygen plus carbon dioxide and radiation therapy of a mouse mammary carcinoma. Cancer, 30, 1154-1158. SUIT, H. D., MAIMORRIS, P., RICH, T. A. and SEDLACEK,
1006
R. S., 1979. Anaesthesia and efficacy of hyperbaric oxygen in radiation therapy. British Journal of Radiology, 52, 244.
Correspondence (The Editors do not hold themselves responsible for opinions expressed by correspondents)
SI units and dimensions of NSD THE EDITOR—SIR,
I think first it is questionable whether the "unit" of NSD—ret—should be so dignified. It is not a physical quantity but a biological effect and, as such, depends on factors the effect of which cannot at present be measured. The dimensions of rad are ML2T~2 M i.e. squared velocity or length times acceleration. The dimensions of ret are (rad/T 011 ), L2T~189. This is for a definite tolerance level which may vary from centre to centre and from one tissue to another. The biological effect of radiation is of two types: 1, that on the normal tissues to which the NSD concept was meant to apply, and 2, that on tumour cells (TSD in ren). The difference between these effects is in the effect of homeostatic control to which the factor T 0 1 1 applies. Besides this, time-lapse allows of recovery by division of cells in both normal tissues and malignant tumours and, as said in the first publication about the NSD concept (Ellis, 1967), this type of recovery does not depend on the essential difference between normal and malignant cells and therefore does not enter into the NSD formula which was derived utilizing that difference. Instead, this type of recovery by cell-division, common to both types of cell, which is uncertain as to the time of its commencement and the rate at which it proceeds, is probably dependent on nutrition, cell-cycle time, oxygenation, temperature and other things so that a full equation should probably be Biological Effect = Dose (rad) Time x F? where F is an unknown and complex factor. The NSD concept being an attempt to separate fractionation from the effect of time in delivering the radiation was clearly a simplified and incomplete theory but its units are nevertheless more complex than those of the rad. On the other hand, the ren has the same dimensions as the rad. The T D F simplification of the NSD concept depends on the NSD formula and on the principle of proportional tolerance embodied in the NSD concept. For example, using the formula, 15 X 200 rad five times a week gives 1127 ret. Twice this is 2254 ret. On the other hand, 30 X 200 five times a week gives 1768 ret. Since the NSD represents a tolerance level, then in comparison wTith 30 fractions at the same rate 1 5 fractions is half the course and £ + £•= 1. To avoid confusion due to imperfect understanding of this proportional (or partial) tolerance principle, the Time Dose Fractionation modification was developed (Orton and Ellis, 1973). TDF = 10- 3 «J l - 538 x- 0169 where x=T/N. The T D F values for various schedules and parts of courses can be added in such a way as to represent similar effects even when adding the effects of fractionated and continuous radiation. The "dimensions" of TDF are: (L2T'~2)1-538(T~0-169) i.e. L 3076 T~ 3 - 245 - -a difficult medical pill for the physicist to swallow. Yours, etc., The Old Bakery, Thames Street, Charlbury, Oxford OX7 3QQ. (Received May 1979)
F. ELLIS.
REFERENCES ELLIS, F., 1967. Fractionation in Radiotherapy. In Modern Trends in Radiotherapy. Ed. Deeley and Wood. Vol. 1 (Butterworth, London). ORTON, C. G. and ELLIS, F., 1973. A simplification in the
use of the NSD in practical radiotherapy. British Journal of Radiology, 46, 529-537.
SI units and dimensions of NSD THE EDITOR—SIR,
My recent letter on the above subject (Greening, 1978) has brought me correspondence from Dr. D. Bewley, Dr. M. Day and Dr. F. Ellis as a result of which I wish to make a small correction to my letter. I wrote: "£> = NSD where t is time and te is a standard value of time. When te is equal to one day y takes the value 0.11." It is this last sentence that is incorrect, as y = 0.11 whatever the standard value of time chosen. I must hasten to add that this does not affect my argument about the dimensions of NSD or the SI units in which it should be expressed. Yours, etc., J. R. GREENING.
The Department of Medical Physics and Medical Engineering, Royal Infirmary, Edinburgh, EH3 9YW. (Received September 1979) REFERENCE GREENING, J. R., 1978. SI units and dimensions of NSD, CRE and TDF. British Journal of Radiology, 5/, 1026.
Biliary rhabdomyosarcoma of childhood THE EDITOR—SIR,
I read with interest the report by Cannon et al., (1979) emphasizing the role of percutaneous transhepatic cholangiography (PTC) in the management of biliary rhabdomyosarcoma of childhood. While agreeing about the importance of early diagnosis of biliary obstruction and particularly of childhood rhabdomyosarcoma, I should like to emphasize the role of less invasive radiological procedures in the management of this rare tumour of childhood. Recently I have seen two young children with rhabdomyosarcoma of the bile ducts. The first had hepatomegaly and had been jaundiced for six weeks when an ultrasound scan showed dilatation of the bile ducts and gall-bladder. Barium studies and PTC were then undertaken to help define the nature and the extent of the obstructing lesion prior to surgery. The appearances on PTC were similar to those described in the case reported by Cannon et al. (1979). The second child had marked hepatic enlargement and had been jaundiced for ten weeks prior to ultrasound scan. This scan showed that the right lobe of the liver had been completely replaced by an enormous mass containing complex echoes resembling "swiss cheese", (Fig. 1). A technetium sulphur colloid scan showed that the mass was intrahepatic, a point not clearly shown on the ultrasound scan. This patient proceeded to subtotal hepatectomy
1005
1979, British Journal of Radiology, 52, 1006
DECEMBER 1979
Correspondence
FIG. 1. Transverse ultrasound scan of the abdomen 7.0 cm above the iliac crest. The mass containing complex echoes and replacing the right lobe of the liver is shown (white arrow), and normal parenchyma in the left lobe of the liver is also shown (black arrow).
without resort to PTC. Indeed had such a procedure been carried out prior to the ultrasound scan the cholangiography needle inevitably would have entered the tumour rather than the bile ducts. Yours, etc., J. B. WITCOMBE.
The Department of Diagnostic Radiology, The Medical School, Oxford Road, Manchester M13 9PT. {Received February 1979)
R. P. HILL, R. S. BUSH.
REFERENCE CANNON, P. M., LEGGE, D. A. and O'DONNELL, B.,
animals anaesthesia with nembutal and, to a smaller extent, urethane can reduce the radiation response of the KHT sarcoma probably as a result of changes in tumour oxygenation. Sheldon et al. (1977) have also shown that nembutal anaesthesia protects the "MT" mouse tumour against radiation damage although in their case protection was greater than could be explained by changes in tumour oxygenation alone. Conversely Suit et al. (1972) found no effect of nembutal anaesthesia when studying a mammary tumour irradiated in air-breathing mice although this may have been because they used a ten-fraction regime. We proposed (Milne et al., 1973) that one explanation for the anomalous effect of anaesthesia during HPO breathing could be that the anaesthesia prevented, wholly or partially, the vasoconstriction which can result from HPO breathing. The difference between the two anaesthetics observed in our experiments could then be explained by the other physiological parameters discussed above which change to a much greater extent following anaesthesia with nembutal than urethane. Suit et al. (1979) suggest in their letter that the vasoconstriction hypothesis is unlikely to explain their results because they found an enhancement factor (TCD50 air/TCDso HPO) of only 1.1 for single dose irradiation under nembutal anaesthesia. We think that this small effect is probably due to the other confounding factors mentioned above and that vasoconstriction and its inhibition by anaesthesia is the major reason for the difference between the results for animals breathing air or HPO. We would agree with Suit et al. (1979) that the clinical experience with HPO may well have been adversely affected by the change from anaesthetized to non-anaesthetized patients, but our results indicate that, because of the interacting physiological factors discussed above, barbiturates are unlikely to be the most appropriate choice for any new study of the role of anaesthesia in the clinical combination of HPO and radiation therapy. Yours, etc.,
1979.
The use of percutaneous transhepatic cholangiography in a case of embryonal rhabdomyosarcoma. British Journal of Radiology, 52, 326-327.
Ontario Cancer Institute, incorporating the Princess Margaret Hospital, 500 Sherbourne Street, Toronto, Ontario, Canada M4X 1K9. {Received May 1979) REFERENCES JOHNSON, R., FOWLER, J. F. and ZANELLI, G. D.,
1976.
Changes in mouse blood pressure, tumor blood flow and core and tumor temperatures following nembutal and urethane anaesthesia. Radiology, 118, 697—703. KRUUV, J. A., INCH, W. R. and MCCREDIE, J. A.,
1967.
Blood flow and oxygenation of tumours in mice. I. Effects of breathing gases containing carbon dioxide at atmospheric pressure. Cancer, 20, 51-70.
Anaesthesia and efficacy of hyperbaric oxygen in radiation therapy THE EDITOR—SIR,
The data presented by Suit et al. in their recent letter (1979) demonstrate one effect that nembutal anaesthesia can have on the radiation response of tumours. Their results are in agreement with our findings from a number of years ago (Milne et al., 1973) that in comparison to no anaesthesia both nembutal and urethane improved oxygenation in the KHT sarcoma when the host animal breathed oxygen at 200 kPa (HPO), with urethane giving a greater improvement than nembutal. This result may be considered somewhat surprising since barbiturates affect the heart and respiration rates of mice and reduce peripheral blood flow and body temperature (Kruuv et al., 1967; Johnson et al., 1976), factors which could lead to a reduction in tumour oxygenation. Indeed we have results (unpublished) indicating that in air-breathing
MILNE, N., HILL, R. P. and BUSH, R. S., 1973.
Factors
affecting hypoxic KHT tumour cells in mice breathing O2, O2 + CO2, or hyperbaric oxygen with or without anaesthesia. Radiology, 106, 663-671. SHELDON, P. W., HILL, S. A. and MOULDER, J. E.,
1977.
Radioprotection by pentobarbitone sodium of a murine tumour in vivo. International Journal Radiation Biology, 32, 571-575. SUIT, H.
D.,
MARSHALL, N.
and
WOERNER, D.,
1972.
Oxygen, oxygen plus carbon dioxide and radiation therapy of a mouse mammary carcinoma. Cancer, 30, 1154-1158. SUIT, H. D., MAIMORRIS, P., RICH, T. A. and SEDLACEK,
1006
R. S., 1979. Anaesthesia and efficacy of hyperbaric oxygen in radiation therapy. British Journal of Radiology, 52, 244.
